ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
NNMT/1-MNA Promote Cell-Cycle Progression of Breast Cancer by Targeting UBC12/Cullin-1-Mediated Degradation of P27 Proteins.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Protein arginine methylation and ubiquitination: A prominent crosstalk and its functions in cancer.Genes & diseases · 2026Review
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- A receptor-Fc based SFV replicon Trim-Away platform for targeted viral protein degradation.Virology journal · 2026Article
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- Detachment-Induced FAK-STAT3-NNMT Inhibits CTCs Anoikis to Promote Breast Cancer Metastasis by Enhancing Fatty Acid Oxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Nicotinamide N-methyltransferase promotes drug resistance in lung cancer, as revealed by nascent proteomic profiling.Molecular oncology · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- An atlas of ferroptosis-induced secretomes.Cell death and differentiation · 2025Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- N7-methylguanosine (m7G) modification in breast cancer: clinical significances and molecular mechanisms.Cancer cell international · 2025Review
- Antisense oligonucleotide targeting nicotinamide N-methyltransferase exhibits antitumor effects.Molecular therapy. Nucleic acids · 2025Article
- PRDX6 Prevents NNMT Ubiquitination and Degradation as a Nonenzymatic Mechanism to Promote Ovarian Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrative Multi-Omics Analysis and Experiments Validation Identify COX5B as a Novel Therapeutic Target for Lung Adenocarcinoma.Oncology research · 2025Article
- CLEC3A Promotes Immune Evasion and Tumor Progression by Enhancing PD-L1 Stability to Weaken T Cell Cytotoxicity in Luminal Breast Cancer.Breast cancer (Dove Medical Press) · 2025Article
- A systematic evaluation of quenching, extraction and analysis procedures for metabolomics study of the mechanism of QYSLD intervention in A549 cells.Analytical and bioanalytical chemistry · 2024Article
- Trim21-mediated CCT2 ubiquitination suppresses malignant progression and promotes CD4Cell death & disease · 2024Article
- NNMT/1-MNA Promote Cell-Cycle Progression of Breast Cancer by Targeting UBC12/Cullin-1-Mediated Degradation of P27 Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Cell cycle dysregulation is a defining feature of breast cancer. Here, 1-methyl-nicotinamide (1-MNA), metabolite of nicotinamide N-methyltransferase(NNMT) is identified, as a novel driver of cell-cycle progression in breast cancer. NNMT, highly expressed in breast cancer tissues, positively correlates with tumor grade, TNM stage, Ki-67 index, and tumor size. Ablation of NNMT expression dramatically suppresses cell proliferation and causes cell-cycle arrest in G0/G1 phase. This phenomenon predominantly stems from the targeted action of 1-MNA, resulting in a specific down-regulation of p27 protein expression. Mechanistically, 1-MNA expedites the degradation of p27 proteins by enhancing cullin-1 neddylation, crucial for the activation of Cullin-1-RING E3 ubiquitin ligase(CRL1)-an E3 ubiquitin ligase targeting p27 proteins. NNMT/1-MNA specifically up-regulates the expression of UBC12, an E2 NEDD8-conjugating enzyme required for cullin-1 neddylation. 1-MNA showes high binding affinity to UBC12, extending the half-life of UBC12 proteins via preventing their localization to lysosome for degradation. Therefore, 1-MNA is a bioactive metabolite that promotes breast cancer progression by reinforcing neddylation pathway-mediated p27 degradation. The study unveils the link between NNMT enzymatic activity with cell-cycle progression, indicating that 1-MNA may be involved in the remodeling of tumor microenvironment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.